One type of treatment for patients having substantially impaired renal function, or kidney failure, is known as “dialysis”. Either blood dialysis (“hemodialysis”) or peritoneal dialysis (PD) methods may be employed. Both methods essentially involve the removal of toxins from body fluids and restoration of such body fluids by diffusion and/or convection by means of a dialysis solution.
Patients receiving hemodialysis typically utilize 75 to 200 liters of prepared dialysis solution three times a week. The largest ingredient in these solutions is water.
Conventionally, dialysis solutions for hemodialysis are prepared from separate concentrated solutions. For example, one concentrate, Preparation A, includes a mixture of varied salts, sugars and acids dissolved in water. Another concentrate, Preparation B, is made of sodium bicarbonate dissolved in water, and may also contain sodium chloride. The constituents must be kept separate until shortly before hemodialysis because of the tendency for insoluble precipitates to form in the combined solution.
Even in concentrated solutions, the Preparations A and B are themselves bulky and difficult to transport. Moreover, bicarbonate solutions such as Preparation B have a tendency to form carbon dioxide and alter the pH of their solution over extended periods of time, even if not mixed with other components. Another logistical problem with preparing dialysis solutions is the need to keep the solutions essentially free of bacteria and endotoxins.
In peritoneal dialysis (PD), the patient's peritoneal cavity is filled with a dialysis solution. The dialysis solution is generally formulated with a high concentration of the dextrose, as compared to body fluids, resulting in an osmotic gradient within the peritoneal cavity. The effect of this gradient is to cause body fluids, including impurities, to pass through the peritoneal membrane and mix with the dialysis solution. By draining the spent dialysis solution from the cavity, the impurities are removed.
In PD, the dialysis solution is administered directly into the patient's body, and it is thus important that the dialysis solution is sterile and maintains the correct proportions and concentrations of components. Conventionally, for PD, dialysis solutions are delivered to the site of administration in pre-mixed solutions.
Similar to dialysis solutions for hemodialysis, the dialysis solutions used in PD are not stable over time due to incompatibility of the components in these solutions. For example, dextrose has a tendency to caramelize in solution over time, and bicarbonate ions react undesirably with calcium and magnesium in solutions to form insoluble calcium carbonate or magnesium carbonate. Bicarbonate can also spontaneously decompose into carbon dioxide and water.
Significant research efforts have been spent on providing dry formulations of components that are subsequently mixed with a solvent, typically water, to form dialysis concentrates or dialysis solutions. The use of dry formulations in the form of powdery material has the potential of increasing shelf life, reduce the formation of possible degradation products, and reduce the weight and volume of the material that needs to be transported to and stored at the dialysis treatment sites.
However, there are difficulties in using dry formulations for preparation of dialysis concentrates and dialysis solutions. For example, the preparation requires careful metering of the different formulations and solvent. It may also be necessary to take measures to ensure proper mixing and dissolution of the dry formulations in the solvent.
U.S. Pat. No. 4,664,891 discloses a system for preparation of a dialysis concentrate from dry chemicals and water. A disposable drum is selectively filled with dry chemicals in different layers, specifically such that an inner core of the drum is loaded with chemicals which form a slurry and/or dissolve slowly. In operation, a spray head is fitted over the drum and water is injected into the drum onto the chemicals within the inner core by the use of a nozzle, whereby the chemicals within the inner core are preferentially dissolved or form a slurry before other chemicals in the drum. Fluid is cycled through the drum until all of the chemicals in the drum have been dissolved and removed.
Another difficulty associated with the use of dry formulations is that certain components of the dry formulations are incompatible and therefore have to be stored separately. Some of the components, e.g. magnesium chloride, calcium chloride and glucose, typically bind water molecules, at least in their commonly used forms, while other components, e.g. NaCl, are hygroscopic. If the former component(s) releases water during storage, the latter component(s) may form lumps or cakes, and these lumps/cakes may be difficult to dissolve when preparing the dialysis solution. If bicarbonates and acids are mixed, gases may be formed in the presence of water. If glucose and acids are mixed and subject to non-dry conditions, the glucose may be degraded and discolored.
Another way to ameliorate the problem is to store the different components in separate packages. However, this leads to an elevated risk for incorrect composition of the dialysis solution due to incorrect handling. Typically, a complicated apparatus needs to be used to ensure proper preparation.
Yet another solution is proposed in US2006/0115395, which discloses an apparatus for producing a peritoneal dialysis solution from dry reagents. The dry reagents are separated into compatible groupings, denoted reagent beds, which are placed in separate compartments within a disposable housing. The disposable housing defines a fluid flow path through the sequence of separate compartments. Each compartment is arranged between an upstream and a downstream compression component, and the reagent beds are constrained from movement within the housing by reagent bed restraints, which have a fine enough porosity to prevent the passage of reagent particles in their dry form while allowing a liquid diluent to pass. In operation, the diluent is fed to the housing to flow along the fluid flow path and dissolve the reagents. The compression components apply continuous compressive force on either side of the reagent bed to pack the reagents close together as the reagent particles are dissolved.
The housing in US2006/0115395 is a disposable of complex design involving a combination of several different materials at significant amounts. The disposable is not only costly and fairly complicated to manufacture, but it may also require non-standard processing for waste handling/recycling. Further, it is not unlikely that the apparatus in US2006/0115395 may produce a dialysis solution of varying composition, since its operation relies on a continuous dissolution of the dry reagents while the diluent flows through the housing. Any lack of dissolution or any accumulation of poorly dissolved reagents in the compression components or on restraints may be difficult to identify by visual inspection.
The prior art also comprises WO2007/144427, which discloses a container that includes a plurality of compartments separated by compartment dividers which rupture when a sufficient pressure is applied by a liquid or gas introduced into the container. Some of the compartments comprises powder which dissolves at the introduction of liquid into the container. The container is a disposable of complex design. Further, the dividers must be designed to open/rupture in a controlled and reproducible way to avoid incomplete dissolution of the powder.
Although the foregoing discussion is given in relation to preparation of dialysis solutions, it is to be understood that corresponding problems and needs are equally and generally valid for the preparation of other types of medical solutions, such as replacement solutions, infusion solutions or nutritional solutions.